This research project extends our analysis of the neuronal response to noxious stimulation of the periphery and nerve injury. Neurons in the dorsal root ganglion and spinal cord represent the first level of processing of neuronal information from the periphery. Using cellular and molecular techniques it is possible to identify important elements in the neuronal networks that subserve the response to nociception, nerve injury and regeneration. The descending control of nociceptive neuronal circuits is being studied in animals with spinal cord transection and inflammation of one hindpaw. Following spinal transection, complete Freund's adjuvant (CFA) hindpaw injection produces edema that is comparable in magnitude to the sham operated control rats. RNA blot analysis of spinal cord dynorphin mRNA regulation identified an 810%, 527% and 500% ipsilateral increase in the spinal transection, sham surgery and naive groups respectively as compared to the contralateral side of the sham surgery group. Immunolabeling of dynorphin immunoreactive cell bodies showed a similar number of neurons in both the spinally transected and sham surgery groups. These data demonstrate that descending afferents to spinal neural circuits partially suppress the dynorphin mRNA and peptide upregulation that occurs in response to peripheral inflammation and hyperalgesia. The aging process includes a variety of physiological and biochemical changes that might impact neuronal processing of noxious inputs. In CFA treated rats of different age groups, the withdrawal of latency of the aged rats (18 months old) was significantly shorter and the edema was greater than that observed in adult animals. This difference was accompanied by significant increase in spinaldynorphin mRNA levels in aged rats. These data indicate that aged rats exhibit a more robust response to painful stimuli resulting in a greater induction of dynorphin mRNA as a result of peripheral inflammation and hyperalgesia.